Antihypertensive dihydropyridines with 1,4,4-trisubstitution.
Dihydropyridines with 1,4,4-trisubstitution were synthesized and tested for antihypertensive activity in a spontaneously hypertensive rat model. This substitution pattern on the dihydropyridine nucleus differs markedly from that found most active in the structure-activity relationship established for nifedipine-like compounds. However, some were found to significantly lower blood pressure at testing doses (30 mg/kg, ip and 100 mg/kg, po) for up to 24 h. Methyl 1,4-dihydro-4,4-dimethyl-1-pyridinepropanoate (2-1), for example, lowered blood pressure 71 mmHg at 30 mg/kg, ip and the effect endured for greater than 24 h. Unlike prototypical dihydropyridines such as nifedipine, these compounds did not seem to have any effect on calcium channels.
Kukla
M J
MJ
Department of Chemical Research, McNeil Pharmaceutical, Spring House, Pennsylvania 19477.
Breslin
H J
HJ
Gill
A
A
D000818:Animals; D000959:Antihypertensive Agents; D055598:Chemical Phenomena; D002621:Chemistry; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy; D015394:Molecular Structure; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D004095:Dihydropyridines